This application requests funding to permit the purchase of a new mass spectrometer that would provide a significant upgrade of the shared instrumentation capabilities available to researchers at the University of Iowa. The proposed instrument will be located in the University of Iowa High Resolution Mass Spectrometry Facility (UIHRMSF), and will be operated and maintained by experienced staff members. The requested instrument is a hybrid quadrupole/orthogonal acceleration time-of-flight (oa- TOF) mass spectrometer capable of performing high-resolution mass spectrometry (HRMS) and HR tandem mass spectrometry (MS/MS) experiments, and will have a liquid chromatography interface. The instrument will be capable of analysis using electrospray, nano-electrospray, and atmospheric pressure chemical ionization methods. Over forty research groups on campus utilize the UIHRMSF, and over thirty of these are involved in biomedical research. The proposed instrument was selected to fulfill current and future needs of the major NIH-sponsored users, as well as other biomedical researchers on campus. Ten NIH-supported projects from eight major users groups described in this proposal provide justification for the acquisition of the proposed mass spectrometer. These projects include structural studies of bioactive natural products from fungi; characterization of novel opioid ligands and their target proteins; analysis of proteins modified by a dopamine metabolite (DOPAL); characterization of novel terpenoid phosphonates and their interactions with RAS proteins; investigation of actin filament conformation using H/D exchange studies; characterization of PEG-peptide conjugates and identification of modification sites in synthetic protein conjugates; synthesis and characterization of natural products and related compounds as potential anticancer and antimalarial agents; and identification of naturally occurring antimicrobial peptides. Access to the state-of-the-art mass spectrometry capabilities of the proposed instrument would be beneficial to all of these research programs. Relevance. The equipment requested in this proposal will be used to support research directed toward the discovery and development of new treatments for cancer, drug dependency, and infectious diseases. Projects dedicated to improving our understanding of periodontal disease, Parkinson's Disease, and various muscular disorders will also benefit from the capabilities of this instrument. [unreadable] [unreadable] [unreadable]